Urine pH and Citrate as Predictors of Calcium Phosphate Stone Formation

KEY POINTS: The occurrence of calcium phosphate stones has increased over the past five decades, and this is most notable in female stone formers. High urine pH and hypocitraturia are the most discriminatory urine parameters between calcium phosphate and calcium oxalate stone formers. High urine pH in calcium phosphate stone formers is independent of the effect of dietary alkali and acid. BACKGROUND: Urinary parameters, including urine pH and citrate, are recognized as critical in the pathophysiology of calcium-based stones. The factors contributing to variation in these parameters between calcium oxalate (CaOx) and calcium phosphate (CaP) stone formers (SFs) are, however, not well-understood. In this study, using readily available laboratory data, we explore these differences to delineate the odds of forming CaP versus CaOx stones. METHODS: In this single-center retrospective study, we compared serum and urinary parameters between adult CaP SFs, CaOx SFs, and non–stone formers. RESULTS: Urine pH was higher and urine citrate lower in CaP SFs compared with same-sex CaOx SFs and non–stone formers. In CaP SFs, higher urine pH and lower citrate were independent of markers of dietary acid intake and gastrointestinal alkali absorption, suggesting abnormal renal citrate handling and urinary alkali excretion. In a multivariable model, urine pH and urine citrate were most discriminatory between CaP SFs and CaOx SFs (receiver-operating characteristic area under the curve of 0.73 and 0.65, respectively). An increase in urine pH by 0.35, a decrease in urine citrate by 220 mg/d, a doubling of urine calcium, and female sex all independently doubled the risk of CaP stone formation compared with CaOx stones. CONCLUSIONS: High urine pH and hypocitraturia are two clinical parameters that distinguish the urine phenotype of CaP SFs from CaOx SFs. Alkalinuria is due to intrinsic differences in the kidney independent of intestinal alkali absorption and is accentuated in the female sex.